Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Androgenic Alopecia

Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Androgenic Alopecia: A Prospective, Randomized, Controlled Clinical Trial

Androgenic Alopecia(AGA) is a highly prevalent condition for which existing pharmacological and surgical interventions present limitations and side effects, creating a clinical need for safer and more effective therapies. In response, human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) have emerged as a cell-free therapeutic strategy. Characterized by their rich bioactive components, absence of tumorigenic risk, and high safety profile, hUCMSC-Exos represent a promising approach for hair regeneration. This study aims to evaluate the safety and efficacy of hUCMSC-Exos combined with automated microneedle delivery for treating AGA. By utilizing innovative lyophilization technology to maintain exosomal bioactivity and employing precision microneedle systems for enhanced delivery, this research seeks to provide a new generation solution for androgenic alopecia treatment.

Androgenic Alopecia (AGA) is a prevalent hereditary condition with significant limitations in current treatment options. Pharmacological therapies are often associated with gender-specific restrictions and adverse effects including sexual dysfunction and hypertrichosis, while surgical and immunotherapeutic approaches face challenges of high cost, limited efficacy, and potential complications. These shortcomings highlight the urgent clinical need for safer and more effective treatment strategies. Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos), nano-scale vesicles measuring 30-150 nm in diameter, present a promising alternative. Enriched with bioactive components including proteins and lipids, these cell-free structures demonstrate no proliferative capacity, tumorigenic risk, or significant cytotoxicity, offering a superior safety profile compared to conventional stem cell therapies. This study employs an innovative "dual-layer membrane lyophilization system" that maintains exosomal bioactivity while enabling room temperature storage and transportation through optimized freeze-drying and reconstitution processes.

To address transdermal delivery challenges, the research utilizes an automated microneedle system that overcomes the limitations of traditional injection and roller microneedle methods in achieving uniform penetration and depth control. This advanced delivery platform ensures precise, consistent, and efficient exosomal permeation into scalp tissues.This study aims to evaluate the safety and efficacy of the combined approach of hUCMSC-Exos and automated microneedle delivery for treating AGA. By integrating innovative lyophilization technology with precision delivery, this research seeks to establish a new generation therapeutic solution for androgenic alopecia.

Inclusion Criteria:

• Male, aged 18 to 60 years (inclusive), in good general health.
• Clinical diagnosis of androgenetic alopecia (AGA) according to the 2023 Chinese Clinical Practice Guideline: Diagnosis and Treatment of Androgenetic Alopecia, with a disease duration of less than 5 years and a Hamilton-Norwood scale classification of stage II to IV at the screening visit.
• Able to fully understand the study's content, procedures, potential benefits, and risks, and willing to provide written informed consent prior to any study-specific procedures.
• Agrees to comply with the study protocol and refrain from using any other treatments for alopecia for the duration of the study.

Exclusion Criteria:

• Unwilling or unable to provide written informed consent.
• History of any malignancy within the past 5 years (except for adequately treated non-scalp basal cell carcinoma or squamous cell carcinoma in situ).
• Hypotension (blood pressure < 90/60 mmHg) documented within 1 month prior to screening, or uncontrolled hypertension within 3 months prior to screening (defined as failure to achieve a target of < 140/90 mmHg while on a stable regimen of at least two antihypertensive medications).
• Known history of any systemic disease that may affect hair growth or confound study assessments (e.g., HIV infection, connective tissue disease, inflammatory bowel disease, hypothyroidism, iron deficiency anemia, malnutrition, syphilis).
• Known history of other forms of non-androgenetic alopecia (e.g., diffuse alopecia, alopecia areata, cicatricial alopecia).
• History of major organ dysfunction, significant autoimmune disease, or immunodeficiency.
• Known coagulation disorders, current use of anticoagulant or antiplatelet therapy (except low-dose aspirin), thrombophilia, or inherited bleeding disorders.
• Treatment with chemotherapy, cytotoxic drugs, scalp radiation, or laser/surgical hair restoration within 12 months prior to screening.
• History of hair transplantation, or need for long-term use of wigs, hairpieces, or hair bonding agents during the trial.
• History of severe or multiple drug allergies, atopy, known allergy to local anesthetics, or planned desensitization therapy during the study period.
• Presence of any active dermatological condition in the target scalp area that could interfere with evaluation (e.g., infection, seborrheic dermatitis, psoriasis, eczema, folliculitis, open wounds, scars, or atrophy).
• Participation in another interventional clinical trial within 4 weeks prior to screening (except for non-interventional studies or participants who only signed the informed consent form without receiving any investigational product).
• Any other medical or psychiatric condition that, in the judgment of the investigator, would compromise the subject's safety, compliance, or suitability for study participation.